Use of Mono-Amine Oxidase Inhibitors to Prevent Herpes Virus Infections and Reactivation from Latency

Posted Jun 15 2010 5:00pm

Description of Invention:Available for licensing are methods of using Monoamine Oxidase Inhibitors (MAOIs) to prevent alpha-herpesvirus lytic infections, such as those caused by Herpes simplex virus (HSV-1 or HSV-2) and Varicella zoster virus (VZV), and to possibly prevent the periodic reactivation of these viruses from latency. MAOIs have been historically used to treat depression, hypertension, and related diseases. The invention describes how MAOIs can also inhibit LSD1, a histone/protein demethylase that is required for initiation of alpha-herpesvirus lytic infection. After an initial lytic infection, alpha-herpesviruses establish latent infections in sensory neurons and undergo periodic reactivation that results in disease ranging from mild lesions to life threatening encephalitis. Investigators have determined that MAOIs may also block the reactivation process. Due to the nature of the target LSD1 and its role in modulating chromatin modifications, these drugs could also prevent infection by or reactivation of other nuclear viruses.

Alpha-herpesviruses infections are common worldwide, with 57% to 80% of adults being seropositive for HSV. Recurrent labial herpes affects roughly one third of the U.S. population, and these patients typically experience 1 to 6 episodes per year. Genital herpes can result from infection with either HSV type and HSV-1 has become an important cause of genital herpes in some developed countries. HSV keratitis is the most frequent cause of corneal blindness in the United States, is a leading indication for corneal transplantation, and is the most common cause of infectious blindness in the Western world.

Applications:

Prevention and treatment of recurrent Herpes simplex virus outbreaks

Prevention and treatment of recurrent Varicella zoster infection

Treatment of HSV encephalitis

Treatment of Herpes keratitis

Development Status:The investigators intend to do a series of in vivo animal studies on the efficacy of MAOIs in preventing primary infection and/or reactivation of herpes simplex virus in a mouse model system.

Collaborative Research Opportunity:The National Institute of Allergy and Infectious Diseases' Laboratory of Viral Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of MAOIs to prevent herpes virus infections and reactivation from latency. Please contact Marguerite J. Miller at 301-435-8619 or millermarg@niaid.nih.gov for more information.